tbuckley/cabot-search huggingface dataset:
RB1-deficient prostate tumor growth and metastasis are vulnerable to ferroptosis induction via the E2F/ACSL4 axis
Authors: Mu-En Wang, Jiaqi Chen, Yi Lu, Alyssa R. Bawcom, Jinjin Wu, Jianhong Ou, John M. Asara, Andrew J. Armstrong, Qianben Wang, Lei Li, Yuzhuo Wang, Jiaoti Huang, Ming Chen
Journal: Journal of Clinical Investigation (2023)

Inactivation of the RB1 tumor suppressor gene is common in several types of therapy-resistant cancers, including metastatic castration-resistant prostate cancer, and predicts poor clinical outcomes. Effective therapeutic strategies against RB1-deficient cancers, however, remain elusive. Here we showed that RB1-loss/E2F activation sensitized cancer cells to ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, by upregulating expression of ACSL4 and enriching ACSL4-dependent arachidonic acid-containing phospholipids, which are key components of ferroptosis execution. ACSL4 appeared to be a direct E2F target gene and was critical to RB1 loss-induced sensitization to ferroptosis. Importantly, using cell line-derived xenografts and genetically engineered tumor models, we demonstrated that induction of ferroptosis in vivo by JKE-1674, a highly selective and stable GPX4 inhibitor, blocked RB1-deficient prostate tumor growth and metastasis and led to improved survival of the mice. Thus, our findings uncover an RB/E2F/ACSL4 molecular axis that governs ferroptosis, and also suggest a promising approach for the treatment of RB1-deficient malignancies.
Steffin DHM, Muhsen IN, Hill LC, et al. Long-term follow-up for the development of subsequent malignancies in patients treated with genetically modified IECs. <i>Blood</i>. 2022;140(1):16-24.
Journal: Blood (2023)

phrase "time of venetoclax" should read "time off venetoclax" in the sentence "In an update from the MURANO study, among 18 response-evaluable patients with a median time of venetoclax of 24 months, the ORR to retreatment was 72%, with 50% of patients remaining on therapy after a median of 11 months."
Analysis of Previous Infection, Vaccinations, and Anti–SARS-CoV-2 Antibody Titers and Protection Against Infection With the SARS-CoV-2 Omicron BA.5 Variant
Authors: Shohei Yamamoto, Tetsuya Mizoue, Norio Ohmagari
Journal: JAMA Network Open (2023)

This cohort study examines whether preinfection anti–SARS-CoV-2 spike antibody titer is associated with protection against Omicron BA.5 infection among staff members of a medical and research center in Tokyo, Japan.
Addressing the Long-term Effects of the COVID-19 Pandemic on Children and Families
Authors: Tumaini R. Coker, Tina L. Cheng, Marci Ybarra
Journal: JAMA (2023)

This Viewpoint discusses a consensus report from the National Academies of Sciences, Engineering, and Medicine (NASEM) that reviews the impact of COVID-19 on the health and well-being of children and families and what needs to be done to attenuate longer-term negative effects.
Obstetric and Neonatal Outcomes Associated With Implementation of a COVID-19 Predelivery Screening Policy in a Taiwan Hospital
Authors: Hui-Chin Lai, Po-Kai Juan, Szu-Ling Chang, Jen-Fu Tsai, Yun-Han Su, Hsiu-Wei Su
Journal: JAMA Network Open (2023)

This cohort study examines obstetric and neonatal outcomes associated with predelivery screening policy implementation aimed to prevent COVID-19 in a Taiwan hospital.
Training in Basic Life Support and Bystander-Performed Cardiopulmonary Resuscitation and Survival in Out-of-Hospital Cardiac Arrests in Denmark, 2005 to 2019
Authors: Theo Walther Jensen, Annette Kjær Ersbøll, Fredrik Folke, Signe Amalie Wolthers, Mikkel Porsborg Andersen, Stig Nikolaj Blomberg, Lars Bredevang Andersen, Freddy Lippert, Christian Torp-Pedersen, Helle Collatz Christensen
Journal: JAMA Network Open (2023)

Strategies to improve survival from out-of-hospital cardiac arrest (OHCA) include mass education of laypersons with no official duty to respond to OHCA. In Denmark, basic life support (BLS) course attendance has been mandated by law in October 2006 for obtaining a driver's license for all vehicles and in vocational education programs.To examine the association between yearly BLS course participation rate and bystander cardiopulmonary resuscitation (CPR) and 30-day survival from OHCA and to examine if bystander CPR rate acted as a mediator on the association between mass education of laypersons in BLS and survival from OHCA.This cohort study included outcomes for all OHCA incidents from the Danish Cardiac Arrest Register between 2005 and 2019. Data concerning BLS course participation were supplied by the major Danish BLS course providers.The main outcome was 30-day survival of patients who experienced OHCA. Logistic regression analysis was used to examine the association between BLS training rate, bystander CPR rate, and survival, and a bayesian mediation analysis was conducted to examine mediation.A total of 51 057 OHCA incidents and 2 717 933 course certificates were included. The study showed that the annual 30-day survival from OHCA increased by 14% (odds ratio [OR], 1.14; 95% CI, 1.10-1.18; P < .001) when BLS course participation rate increased by 5% in analysis adjusted for initial rhythm, automatic external defibrillator use, and mean age. An average mediated proportion of 0.39 (95% QBCI, 0.049-0.818; P = .01). In other words, the last result indicated that 39% of the association between mass educating laypersons in BLS and survival was mediated through an increased bystander CPR rate.In this cohort study of Danish BLS course participation and survival, a positive association was found between annual rate of mass education in BLS and 30-day survival from OHCA. The association of BLS course participation rate on 30-day survival was mediated by the bystander CPR rate; approximately 60% of the association of BLS course participation rate on 30-day survival was based on factors other than increased CPR rates.
High Levels of Antidrug Antibodies Against Atezolizumab as a Predictive Marker for Clinical Outcomes in Patients With Hepatocellular Carcinoma
Authors: Yasuyuki Shigematsu, Kentaro Inamura
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Evaluation of Employment Loss and Financial Hardship Among US Adults With Disabilities During the COVID-19 Pandemic
Authors: Oliver T. Nguyen, Juhan Lee, Amir Alishahi Tabriz, Young-Rock Hong, Mohammed Al Jumayli, Maija Reblin, Kea Turner
Journal: JAMA Network Open (2023)

This cross-sectional study estimates the prevalence and determinants of employment loss and financial hardship among adults with disabilities during the COVID-19 pandemic.
JAMA Network Open—The Year in Review, 2022
Authors: Stephan D. Fihn, Frederick P. Rivara
Journal: JAMA Network Open (2023)

Last year was another tumultuous year, with the evolution of SARS-CoV-2, ongoing war and destruction in Ukraine, economic hardship throughout the world, mind-numbing recurrences of racial and ethnic violence, accumulating evidence of the devastating effects of climate change, and wide political and social divisions.At the same time, there have been positive developments regarding management of COVID-19, including new treatments for COVID-19 to replace ones no longer effective, increasing immunity among many populations from immunization and infection, and increasing recognition of the need to understand and treat post-COVID-19 condition symptoms.These circumstances and events have served to further energize the editors and staff of JAMA Network Open to pursue our mission "to improve health, health care, and health equity worldwide through open access dissemination of high quality, innovative, general medical research and commentary by and for a broad range of clinicians, researchers, policy makers, and public health and health care leaders."We remain deeply committed to addressing racism in medicine, health care, and society both in the US and abroad. 1,2Monica Vela, MD, joined us this year as JAMA Network Open Diversity, Equity, and Inclusion associate editor.In this role, she collaborates with the rest of the editors and with Preeti N. Malani, MD, MSJ, Director of Equity for the JAMA Network, to lead implementation of the journal's plan to improve diversity of our editors, authors, and reviewers; assist new authors in publishing their work; train the next generation of editors from diverse backgrounds; and publish the highest quality studies related to diversity, equity, and inclusion.][6][7][8][9][10] We received nearly 13 000 research manuscripts in 2022, an increase of 18% from 2021.We have also increased the number of published articles to approximately 8 per weekday, holding our acceptance rate at 15%.Approximately 3000 of these submissions were related to the COVID-19 pandemic, forcing us to be highly selective to ensure that those we now publish provide important new information.
Inferior Vena Cava Filter Retrieval Rates Associated With Passive and Active Surveillance Strategies Adopted by Implanting Physicians
Authors: Emily Sterbis, Jonathan Lindquist, Alexandria Jensen, Michael Hong, Shane Gupta, Robert Ryu, P. Michael Ho, Premal Trivedi
Journal: JAMA Network Open (2023)

Inferior vena cava filters are commonly implanted and infrequently retrieved. Nonretrieval contributes to significant morbidity, motivating US Food and Drug Administration and multisociety communications emphasizing the need for improved device surveillance. Current guidelines suggest that implanting physicians and referring physicians should be responsible for device follow-up, but it is not known whether shared responsibility contributes to lower retrieval.To determine if primary responsibility for follow-up care assumed by the implanting physician team is associated with increased device retrieval.This retrospective cohort study examined a prospectively collected registry of patients with inferior vena cava filters implanted from June 2011 to September 2019. Medical record review and data analysis was completed in 2021. The study included 699 patients who underwent implantation of retrievable inferior vena cava filters at an academic quaternary care center.Prior to 2016, implanting physicians had a passive surveillance strategy whereby letters highlighting indications for and the need for timely retrieval were mailed to patients and ordering clinicians. Starting in 2016, implanting physicians assumed active responsibility for surveillance, whereby candidacy for device retrieval was assessed periodically via phone calls and retrieval scheduled when appropriate.The main outcome was the odds of inferior vena cava filter nonretrieval. Within regression modeling of the association between the surveillance method and nonretrieval, additional covariates of patient demographics, concomitant malignant neoplasm, and presence of thromboembolic disease were included.Of the 699 patients who received retrievable filter implants, 386 (55.2%) were followed up with passive surveillance, 313 (44.8%) with active surveillance, 346 (49.5%) were female, 100 (14.3%) were Black individuals, and 502 (71.8%) were White individuals. The mean (SD) age at filter implantation was 57.1 (16.0) years. Mean (SD) yearly filter retrieval increased following the adoption of active surveillance, from 190 of 386 (48.7%) to 192 of 313 (61.3%) (P < .001). Fewer filters were deemed permanent in the active group vs passive group (5 of 313 [1.6%] vs 47 of 386 [12.2%]; P < .001). Age at the time of implantation (OR, 1.02; 95% CI, 1.01-1.03), concomitant malignant neoplasm (OR, 2.18; 95% CI, 1.47-3.24), and passive contact method (OR, 1.70; 95% CI, 1.18-2.47) were associated with increased odds of filter nonretrieval.The findings of this cohort study suggest that active surveillance by implanting physicians is associated with improved inferior vena cava filter retrieval. These findings support encouraging physicians who implant the filter to take primary responsibility for tracking and retrieval.
Pembrolizumab Added to Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Relapsed or Refractory Classic Hodgkin Lymphoma
Authors: Locke J. Bryan, Carla Casulo, Pamela B. Allen, Scott E. Smith, Hatice Savas, Gary L. Dillehay, Reem Karmali, Barbara Pro, Kaitlyn L. Kane, Latifa A. Bazzi, Joan S. Chmiel, Brett A. Palmer, Jayesh Mehta, Leo I. Gordon, Jane N. Winter
Journal: JAMA Oncology (2023)

To our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant.
Ann Robinson’s research reviews—16 March 2023
Authors: Ann Robinson
Journal: BMJ (2023)

AML: markers on the road to cure?Acute myeloid leukaemia (AML) is a cruel disease: 85% of those diagnosed will be dead within five years.Treatment usually consists of chemotherapy to achieve remission, often followed by stem cell transplant for those at highest risk of relapse.Stem cell transplant greatly increases the chance of survival and can be curative, but having a transplant is no picnic and it needs to be reserved for those most likely to benefit.
Downregulation of Hsp90 and the antimicrobial peptide Mtk suppresses poly(GR)-induced neurotoxicity in C9ORF72-ALS/FTD
Authors: Soojin Lee, Yong-Woo Jun, Gabriel R. Linares, Brandon Butler, Yeliz Yuva-Adyemir, Jill Moore, Gopinath Krishnan, Bryan Ruiz-Juarez, Manuel Santana, Marine Pons, Neal Silverman, Zhiping Weng, Justin K. Ichida, Fen-Biao Gao
Journal: Neuron (2023)

GGGGCC repeat expansion in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat RNAs can be translated into dipeptide repeat proteins, including poly(GR), whose mechanisms of action remain largely unknown. In an RNA-seq analysis of poly(GR) toxicity in Drosophila, we found that several antimicrobial peptide genes, such as metchnikowin (Mtk), and heat shock protein (Hsp) genes are activated. Mtk knockdown in the fly eye or in all neurons suppresses poly(GR) neurotoxicity. These findings suggest a cell-autonomous role of Mtk in neurodegeneration. Hsp90 knockdown partially rescues both poly(GR) toxicity in flies and neurodegeneration in C9ORF72 motor neurons derived from induced pluripotent stem cells (iPSCs). Topoisomerase II (TopoII) regulates poly(GR)-induced upregulation of Hsp90 and Mtk. TopoII knockdown also suppresses poly(GR) toxicity in Drosophila and improves survival of C9ORF72 iPSC-derived motor neurons. These results suggest potential novel therapeutic targets for C9ORF72-ALS/FTD.
A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Authors: H. Josh Jang, Galen Hostetter, Alexander W. Macfarlane, Zachary Madaj, Eric A. Ross, Toshinori Hinoue, Justin R. Kulchycki, Ryan S. Burgos, Mahvish Tafseer, R. Katherine Alpaugh, Candice L. Schwebel, Rutika Kokate, Daniel M. Geynisman, Matthew R. Zibelman, Pooja Ghatalia, Peter W. Nichols, Woonbok Chung, Jozef Madzo, Noah M. Hahn, David I. Quinn, Jean-Pierre J. Issa, Michael J. Topper, Stephen B. Baylin, Hui Shen, Kerry S. Campbell, Peter A. Jones, Elizabeth R. Plimack
Journal: Clinical Cancer Research (2023)

Abstract Purpose: On the basis of preclinical evidence of epigenetic contribution to sensitivity and resistance to immune checkpoint inhibitors (ICI), we hypothesized that guadecitabine (hypomethylating agent) and atezolizumab [anti–programmed cell death ligand 1 (PD-L1)] together would potentiate a clinical response in patients with metastatic urothelial carcinoma (UC) unresponsive to initial immune checkpoint blockade therapy. Patients and Methods: We designed a single arm phase II study (NCT03179943) with a safety run-in to identify the recommended phase II dose of the combination therapy of guadecitabine and atezolizumab. Patients with recurrent/advanced UC who had previously progressed on ICI therapy with programmed cell death protein 1 or PD-L1 targeting agents were eligible. Preplanned correlative analysis was performed to characterize peripheral immune dynamics and global DNA methylation, transcriptome, and immune infiltration dynamics of patient tumors. Results: Safety run-in enrolled 6 patients and phase II enrolled 15 patients before the trial was closed for futility. No dose-limiting toxicity was observed. Four patients, with best response of stable disease (SD), exhibited extended tumor control (8–11 months) and survival (&amp;gt;14 months). Correlative analysis revealed lack of DNA demethylation in tumors after 2 cycles of treatment. Increased peripheral immune activation and immune infiltration in tumors after treatment correlated with progression-free survival and SD. Furthermore, high IL6 and IL8 levels in the patients’ plasma was associated with short survival. Conclusions: No RECIST responses were observed after combination therapy in this trial. Although we could not detect the anticipated tumor-intrinsic effects of guadecitabine, the addition of hypomethylating agent to ICI therapy induced immune activation in a few patients, which associated with longer patient survival.
High Levels of Antidrug Antibodies Against Atezolizumab as a Predictive Marker for Clinical Outcomes in Patients With Hepatocellular Carcinoma—Reply
Authors: Chan Kim, Hannah Yang, Hong Jae Chon
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma
Authors: Susana Banerjee, Gaia Giannone, Andrew R. Clamp, Darren P. Ennis, Rosalind M. Glasspool, Rebecca Herbertson, Jonathan Krell, Ruth Riisnaes, Hasan B. Mirza, Zhao Cheng, Jacqueline McDermott, Clare Green, Rebecca S. Kristeleit, Angela George, Charlie Gourley, Liz-Anne Lewsley, Debbie Rai, Udai Banerji, Samantha Hinsley, Iain A. McNeish
Journal: JAMA Oncology (2023)

Importance Patients with platinum-resistant or refractory ovarian high-grade serous carcinoma (PR-HGSC) have a poor prognosis and few therapeutic options. Preclinical studies support targeting PI3K/AKT/mTOR signaling in this setting, and a phase 1 study of the dual mTORC1/mTORC2 inhibitor vistusertib with weekly paclitaxel showed activity. Objective To evaluate whether the addition of vistusertib to weekly paclitaxel improves clinical outcomes in patients with PR-HGSC. Design, Setting, and Participants This phase 2, double-blind, placebo-controlled multicenter randomized clinical trial recruited patients from UK cancer centers between January 2016 and March 2018. Patients with PR-HGSC of ovarian, fallopian tube, or primary peritoneal origin and with measurable or evaluable disease (Response Evaluation Criteria in Solid Tumors version 1.1 and/or Gynecological Cancer Intergroup cancer antigen 125 criteria) were eligible. There were no restrictions on number of lines of prior therapy. Data analysis was performed from May 2019 to January 2022. Interventions Patients were randomized (1:1) to weekly paclitaxel (80 mg/m 2 days 1, 8, and 15 of a 28-day cycle) plus oral vistusertib (50 mg twice daily) or placebo. Main Outcomes and Measures The primary end point was progression-free survival in the intention-to-treat population. Secondary end points included response rate, overall survival, and quality of life. Results A total of 140 patients (median [range] age, 63 [36-86] years; 17.9% with platinum-refractory disease; 53.6% with ≥3 prior therapies) were randomized. In the paclitaxel plus vistusertib vs paclitaxel plus placebo groups, there was no difference in progression-free survival (median, 4.5 vs 4.1 months; hazard ratio [HR], 0.84; 80% CI, 0.67-1.07; 1-sided P = .18), overall survival (median, 9.7 vs 11.1 months; HR, 1.21; 80% CI, 0.91-1.60) or response rate (odds ratio, 0.86; 80% CI, 0.55-1.36). Grade 3 to 4 adverse events were 41.2% (weekly paclitaxel plus vistusertib) vs 36.7% (weekly paclitaxel plus placebo), and there was no difference in quality of life. Conclusions and Relevance In this randomized clinical trial of weekly paclitaxel and dual mTORC1/2 inhibition in patients with PR-HGSC, vistusertib did not improve clinical activity of weekly paclitaxel. Trial Registration isrctn.org Identifier: ISRCTN16426935
Nano-based approaches for diagnosis and therapy of gastric cancer
Authors: Arya Rai, Shristhi S. Rawat, Hitesh Chopra, Inderbir Singh, Talha B. Emran
Journal: International Journal of Surgery (2023)

Rai, Arya M.Pharma; Rawat, Shristhi S. M.Pharma; Chopra, Hitesh PhDa; Singh, Inderbir PhDa; Emran, Talha B. PhDb,c, Author Information
Death-associated with human monkeypox outbreak 2022: the current perspectives – correspondence
Authors: Masoud Keikha, Mehdi Zandhaghighi, Shahram Shahraki Zahedani
Journal: International Journal of Surgery (2023)

Keikha, Masoud PhD; Zandhaghighi, Mehdi PhD; Shahraki Zahedani, Shahram PhD Author Information